Abstract 76: Intra-Placental Gene Transfer of Human Insulin-Like Growth Factor-1 Prevents Obesity in an Intra- Uterine Growth Restricted Model Exposed to High Fat Diet Postnatally
We have shown that mesenteric uterine artery ligation in mice significantly reduces fetal birth weight (IUGR) and increases risk of adult onset of hypertension and obesity, which are all reversed by adenoviral mediated hIGF1 (Ad hIGF1) intraplacental gene transfer. We hypothesized that intraplacental Ad hIGF1 in IUGR mice prevents adult onset of obesity even when challenged with environmental stress as fat diet. Laparotomy was done at day 18 on pregnant C57BL/6J mice and divided into 3 groups (n= 16). Control: Sham operated; IUGR: birth weight <10% for gestational age; Treated: IUGR+IGF-1. Pups were delivered on day 20, cross fostered to CD1 mice, sorted by gender at 4 weeks. At 8 weeks, high fat diet (45% fat) was introduced and mice were followed up to 24 weeks. Body weight, fat pad, fasting serum leptin and food consumption were measured. Data analyzed by Chi-square or ANOVA and stratified by sex Compared to sham, IUGR significantly decreases birth weight, which is restored to normal in IUGR+IGF-1(1.12± .1 vs 0.9± .1 vs 1.09± .1 g, p=0.001). Mean body weight differences among the groups persist till 8 weeks. By 14 weeks, male IUGR mice had significant weight gain(obese) compared to sham and treatment groups (fig A). Same trend was seen in female IUGR at 18 weeks. Total fad pad weights were significantly higher in IUGR compared to SHAM, restored to normal in IUGR+IGF-1 (fig B). Compared to sham, IUGR significantly increases fasting serum leptin, restored to normal in IUGR+IGF-1 (2.4±0.2 vs 7.9±1.5 vs 3.4±0.4 pg/ug, p= .01) Our results demonstrate that intraplacental gene transfer with Ad-hIGF-1 reprograms the IUGR fetus and attenuates the risk of adult onset of obesity under environmental stress
- © 2012 by American Heart Association, Inc.